During the past three decades, a considerable amount of information has been collected on the primary role exerted by neurogenic mechanisms in the development and progression of several cardiovascular and non-cardiovascular disease. However, the information available is not limited to the pathophysiological background of a given disease, but, in some instances, also relates to the prognostic significance of the reported sympathetic abnormalities. The evidence collected so far on this issue can be summarized as shown in Fig. 1.
First, in patients with congestive heart failure, indirect and direct markers of systemic and regional sympathetic drive (heart rate variability, heart rate spectral power, venous plasma noradrenaline, cardiac and renal noradrenaline spillover) have been demonstrated to bear a close and direct relationship with cardiovascular mortality, disease progression and arrhythmic events, including sudden death [1–8]. Similar conclusions can be drawn from an analysis of the results of studies aimed at assessing the prognostic value of plasma noradrenaline or heart rate variability in post-stroke phases, following an acute myocardial infarction or in patients with vasospastic angina [9–12]. Finally, the prognostic relevance of a dysfunction in sympathetic cardiovascular control has also been described in non-cardiovascular diseases, such as in diabetes mellitus and in renal failure [13,14], thereby documenting the clinical relevance of the neuroadrenergic overdrive in a broad spectrum of pathological states.
Surprisingly, no data are available on the prognostic significance of sympathetic dysfunction in hypertension. This lack of information has a number of plausible explanations, including evidence that: (i) the incidence of adverse events, as well as the cardiovascular or non-cardiovascular mortality rate, is much lower in the hypertensive state than in heart failure, stroke or myocardial infarction ; (ii) the degree of sympathetic activation, and thus the ability of the available techniques to detect small alterations in adrenergic drive, is less in hypertension than in the above-mentioned cardiovascular disease ; and (iii) sympathetic dysfunction shows an interindividual variability that is higher in the hypertensive population than in heart failure or post-myocardial infarction patients . The lack of information also applies to prospective evidence on the role of sympathetic factors in the development of hypertension-related end-organ damage, such as arterial and arteriolar structural and functional abnormalities and left ventricular hypertrophy, as well as renal insufficiency and failure.
In the present issue of the journal, Strand et al.  provide prospective information on the ability of arterial noradrenaline to predict the development of hypertension-related cardiac structural changes (i.e. left ventricular hypertrophy).
Adrenergic drive and cardiac hypertrophy: from experimental studies to prospective evidence
There is solid evidence to support the concept that sympathetic neural mechanisms participate in the development and progression of left ventricular hypertrophy. Studies performed in vitro have indeed shown that the growth of cardiomyocytes is under adrenergic influences . The ‘prohypertrophic’ effects exerted by the sympathetic nervous system on myocardial tissue have been confirmed in animal studies showing that the systemic infusion of noradrenaline for several weeks, even when devoid of any pressor effect, triggers an increase in left ventricular mass . The evidence collected to date also extends to human beings. This because it has been reported that, in hypertensive patients, a coronary arterovenous difference in plasma noradrenaline is enhanced in the presence of the left ventricular hypertrophy , thereby indicating that the hypertrophic heart is associated with (and probably dependent on) an increased adrenergic cardiovascular drive. Furthermore, in hypertensive patients with echocardiographic evidence of left ventricular hypertrophy: (i) cardiac noradrenaline spillover is increased  and (ii) sympathetic neural discharge, as quantified by the microneurographic approach, is enhanced . Finally, in conditions characterized by a marked sympathetic activaction, such as in the hypertensive state complicated by end-stage renal failure, venous noradrenaline (i.e. an indirect marker of adrenergic drive) also displays an increase in its circulating blood levels .
The study by Strand et al.  supports the above-mentioned findings by showing that arterial noradrenaline is capable of predicting left ventricular mass index (and the occurrence of left ventricular hypertrophy) in patients who became hypertensive during the 20-year follow-up period of the study. Interestingly, the ability of arterial noradrenaline values to predict left ventricular mass was independent of blood pressure and body mass index (i.e. two variables closely related to cardiac structural changes associated with high blood pressure) .
Left ventricular hypertrophy, haemodynamic profile and effects of treatment
The study by Strand et al.  offers the chance to briefly discuss three other issues. First, no correlation between heart rate and arterial noradrenaline was found in their study. Although, in some previous studies, a significant relationship has been reported between these two variables in hypertension [25,26], no relationship between heart rate and microneurographically recorded sympathetic nerve traffic has been found in a large group of patients . Second, in the study by Strand et al. , 24-h ambulatory blood pressure monitoring was performed only at follow-up examination. This meant that the authors were unable to confirm the superiority of ambulatory blood pressure over office blood pressure in reflecting the presence of hypertension-related cardiac organ damage [28–30]. Finally, the results of Strand et al.  raise the question of whether arterial noradrenaline is capable of reflecting changes in cardiac mass triggered by antihypertensive treatment. It is hoped that future studies will provide an answer to this clinically relevant question.
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